Evidence has accumulated suggesting that women who take estrogens after the menopause have decreased rates of arteriosclerosis. The proposed research will investigate the effects of estrogen with and without progestin on several major influences on arteriosclerosis: concentration and metabolism of the plasma lipoproteins, blood pressure and vascular responsiveness to pressors and the activity of the hemostatic system. The overall goals are, 1) to determine the dose of estrogens that could favorably alter risk factors for vascular disease and 2) to understand the mechanisms of action of estrogen. Two prospective studies are proposed. Each will involve administering sex hormones for 3 month periods to healthy postmenopausal women in a placebo controlled double-blind crossover design. Each subject will thus serve as her own control. 1. Estrogen alone. Thirty subjects will receive conjugated equine estrogens (Premarin) 0.3mg, 0.6mg, and 1.25mg daily. 2. Estrogen with progesterone. Using the results of the previous trial, 30 women will receive an estrogen alone and with cyclical administration of progesterone. In these protocols, the following variables will be measured: a) detailed lipid and apoprotein analysis of the lipoproteins VLDL, LDL, HDL2 and HDL3; b) Lipid metabolism: Hepatic and extrahepatic lipoprotein lipases which control HDL metabolism; LDL receptors and cholesterol synthesis in the subjects' blood mononuclear cells, and VLDL subfractions and the direct uptake of the subjects' VLDL by cultured macrophages; c) blood pressure on multiple occasions at home and in clinic; d) vascular resistance and reactivity to angiotensin and norepinephrine; and e) indices of hypercoagulability such as prothrombin activation fragment, protein C, thrombin-antithrombin complex, and fibrinopeptide A. Knowledge gained from these studies may provide information for rational prescribing of estrogens to postmenopausal women.
Showing the most recent 10 out of 18 publications
